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CONCLUSIONS: In analyses of biomarkers and composite subtypes for prognosis studies such as in breast cancer, the use of compatible imputation models and penalization methods is recommended for MC modeling in samples with low event numbers and/or with covariate imbalance.

Breast cancer brain metastasis (BCBM) is a devastating disease with limited treatment options, largely due to the presence of the blood-brain barrier (BBB) in the central nervous system (CNS), and thus, the development of effective alternative therapies for BCBM remains a significant unmet clinical challenge. Herein, we found that monocytes, M2 macrophages, and adrenomedullin (AM) were abundantly present in human BCBM. Therefore, we innovatively proposed monocytes/macrophages as promising...

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a Cytosine-Adenosine-Guanine (CAG) repeat expansion in the Huntingtin (HTT) gene, with no disease-modifying therapies currently available. The precise molecular function of the HTT protein is unclear, and the lack of selective chemical tools has limited functional studies. We have identified and characterized macrocyclic peptide binders targeting HTT. These binders exhibit low-nanomolar affinity in vitro and engage...

BACKGROUND: Although severe maternal morbidity (SMM), such as severe hemorrhage and sepsis, can occur from conception to 6 weeks postpartum, most surveillance studies in Canada are restricted to intrapartum cases, with rates approximating 17 per 1000 births. We aimed to characterize the frequency of SMM from conception to 6 weeks postpartum and describe its associations with maternal and clinical characteristics.

CONCLUSION: MRI-based machine learning models may support noninvasive prediction of BRAF mutation status in pLGG. FLAIR is the best-predicting single sequence, but multisequence integration was associated with improved and more balanced performance. These findings support multisequence radiomics as a promising tool to guide precision treatment in pLGG, particularly when tissue sampling is not feasible.

CONCLUSIONS: This pooled analysis provides limited evidence of an association between occupational exposure to chlorinated solvents and lung cancer, though exposure-response trends were noted among exposed individuals.

Despite promising data showing that circulating tumour DNA (ctDNA) dynamics during treatment can inform real-time tumour response and recurrence risk¹, how best to translate these insights into actionable clinical decision-making remains unclear. Here we report results from the EP-STAR trial-a multi-centre, ctDNA-driven, risk-adapted, non-randomized phase II study ( NCT04072107 ; ClinicalTrials.gov) testing whether a risk-adaptive treatment (RAT) strategy guided by on-treatment ctDNA dynamics...

CONCLUSIONS: By integrating multidimensional data, our framework enables the tailored prognostication and clinical decision to meet the multidimensional requirements of research and medicine.

Medulloblastoma (MB) is a biologically and clinically heterogeneous pediatric brain tumor. However, large-scale molecular subgrouping studies have mainly been conducted in Western populations, and comprehensive data from Asia are limited. To address this gap, we analyzed 242 MB cases collected from 39 institutions through the Japan Pediatric Molecular Neuro-Oncology Group, performing centralized molecular classification using NanoString-based gene expression profiling, DNA methylation arrays,...

Current nucleic acid preservation relies on ultra-low temperature storage (-20°C to -80°C), imposing significant infrastructure, cost, and accessibility barriers that limit genomic medicine worldwide. We present a comprehensive evaluation of ensilication, a silica-based encapsulation method enabling ambient-temperature preservation of DNA without compromising sequencing fidelity. Across clinical, genomic, and biochemical analyses, ensilication maintained complete diagnostic concordance with...

TDP-43 and FUS are RNA-binding proteins involved in the regulation of diverse RNA processing events and have been strongly implicated in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We have previously demonstrated the role of symmetrical dimethylation (me2s) of a conserved arginine residue (R1810 in human POLR2A) in the C-terminal domain (CTD) of RNA polymerase II (RNAPII), which facilitates the recruitment of the Tudor...

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CONCLUSION: Based on the clinical and genetic data, the present familial study revealed the plausible contribution of a novel variant of RELN in association with BD in the affected family. The present study's findings are valuable in understanding the genetic basis of the multifactorial phenotype BD and pave a better path for future functional studies.

BackgroundReliable detection of huntingtin (HTT) is essential for understanding Huntington's disease (HD) biology and for evaluating therapeutic strategies. However, high-quality monoclonal antibodies (mAbs) against the HTT C-terminal domain remain limited.ObjectiveWe sought to generate and validate novel monoclonal antibodies targeting the HTT C-terminal HEAT-containing domain to better detect HTT independently of potential effects of polyglutamine length that can impact some N-terminally...

Although the genetic code is degenerate, codon selection is nonrandom and reflects significant functional constraints. Codon-usage bias (CUB) acts as a layer of post-transcriptional regulation, influencing messenger RNA (mRNA) stability, translation kinetics, and co-translational protein folding. While CUB is well-characterized in unicellular organisms, its regulatory scope and functional consequences in humans remain complex and less defined. Our study offers a comprehensive evaluation of human...

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Digital, self-guided, single-session interventions (SSIs) deliver structured psychological support within one interaction. Here we crowdsourced 66 diverse 10-min SSIs for depression and, with input from researchers and lived-experience experts, selected 11 for testing in a preregistered online randomized controlled trial (ClinicalTrials.gov ID: NCT06856668 ). US adults (N = 7,505) experiencing elevated depressive symptoms were randomly assigned to 1 of the 11 crowdsourced SSIs, a validated...

CONCLUSIONS: Real-world data from the Canadian population suggest a low level of long-term persistence on selexipag, although the level of persistence is similar to reported rates for other PAH therapies. Further research into predictors of selexipag persistence is needed to help optimize potential treatment outcomes.

CONCLUSION: A population-based approach provided new evidence for accumulating illnesses over young adulthood, supporting the need for novel models of anticipatory care for adults with 22q11.2 microdeletion. A similar genetics-first strategy, defining cohorts with shared genetic changes, may facilitate understanding of premature aging mechanisms relevant to the general population.

RESEARCH AIMS: The benefits of parenting interventions for child and family outcomes following pediatric brain injury are well documented. However, training in pediatric neuropsychology largely emphasizes a focus on assessment, as well as syndrome- or disorder-specific interventions. Greater attention to transdiagnostic intervention is warranted, particularly pediatric neurorehabilitation programs that are family-centered and evidence-based. This study evaluated the acceptability of a didactic...